Monosodium Glutamate and Autism Revisited

Those who have been following my discussions on my last post regarding monosodium glutamate and the claimed link between it and autism may know that I have had some pretty spirited comments regarding the subject.  Part of it came from my admitted lack of understanding of what MSG actually does in the body once it was ingested.  A few comments later, I was set right with several clinical studies on the compound, and it's relationship to the nervous system.  So, in light of the new evidence, I thought I would make a new post to outline what I have learned, and what still needs to be proven before I accept MSG as the "smoking gun" in all autism cases.  

I would also like to point out that I do not oppose the elimination of MSG as an additive in all it's forms from the food supply.  There are too many people that are adversely effected by this compound (most notably those that suffer with Fragile X Syndrome) to have it as such a general additive.  If you can't make your food taste good naturally, perhaps you shouldn't be selling it.

First, it is necessary to understand the glutamate compound.  Glutamate is one of four major components of DNA, as well as being one of the most (if not the most) important neurotransmitter protein in the brain.  Without glutamate in our body, we would die.  

That being said, most natural sources of glutamate are found in a bonded form with other proteins, which take longer to introduce into the system.  Common sources are protein foods like meat, eggs, dairy products, traditionally processed foods (like real cheese and tofu), and tomatoes.  The levels of glutamate in these foods are fairly low compared to the additives that are put in our processed and packaged food supply.  

The research that I have found shows damage to the brain at the hypothalamus (Olney, ournal of Neuropathology & Experimental Neurology. 31(3):464-488, July 1972). Another article points out that retina damage occurred in mice when exposed to high doses of MSG (Olney, Annu. Rev. Pharmacol.
Toxicol. 1990. 30:47-71). Neither mention other parts of the brain, those that are protected by the blood brain barrier.  

It should be noted that Dr. Olney has been key to the banning of monosodium glutamate in baby food back in the 1970's.  His work is groundbreaking, and invaluable in understanding the effects of MSG when ingested in significant quantities.

By contrast, patients in an MRI study with autism exhibited increase in gray matter in medial and dorsolateral frontal areas, in the lateral and medial parts of the temporal lobes, in the parietal lobes, cerebellum and claustrum. Patients also showed decrease in frontal, parietal, temporal and occipital white matter (Bonilha, Elsevier Brain and Development, the Official Journal of the Japanese Society of Child Neurology, Received 14 June 2007; received in revised form 25 November 2007; accepted 26 November 2007).  In Dr. Olney's study, only the hypothalamus and retina tissue was impacted in developing infants.  

Also, the abnormally developed amygdala and medial temporal lobe have been detected in patients with autism through MRI scans, suggesting a lack of developmental neuronal pruning (or incomplete pruning) as the cause of autism (Howard, NeuroReport:Volume 11(13)11 September 2000p 2931-2935). And the link between the amygdala and autism has also been established (Amaral, Novartis Foundation Symposium 251, “Autism: Neural Basis and Treatment Possibilities”, June 2002).

And so the link between increased brain size in multiple regions, reduced or non-existent neuronal pruning, and autism have been made.  Most neuropsychologists that I have known or read about subscribe to this link for most cases of irreversible autism as opposed to allergy autism, but more on that later.  

Now genetics step in with recent research on the PTEN and Serotonin Transmitter genes resulting in increased brain growth (Page, PNAS February 10, 2009 vol. 106 no. 6 1989-1994). Each of these genes increase brain size, while a combination of both compound the brain growth.  

Also recently announced was a link between brain growth, brain development, gastrointestinal repair, and the MET gene.  It seems that 118 of the 214 families studied had this same genetic link between autism and gastrointestinal disorders (Campbell, A genetic variant that disrupts METtranscription is associated with autism, PNAS 2006 103:16621-16622; published online before print October 30, 2006, doi:10.1073/pnas.0608027103).  While this could only be conceivably linked to a cause of autism in 30% of all cases, it is another genetic piece of the puzzle.

I found a reference to the Nerve Growth Factor (NGF) and inflamed sensory nerves, or nerves that receive a stimulation of some sort outside of the nervous system (vision, touch, etc.). They do see an increase in NGF within a location irritated by a stimulus in those sensory nerves. The hypothesis is that nerve growth in the brain would be related to an increase of NGF in the system which would be caused by MSG, though they only observed an increase in neuropeptide production when using another stimulus, and MSG was not mentioned in the article (Bradley et al, Int Arch Allergy Immunol 1999;118:150-153). The hypothesis has not been tested, as far as I have been able to determine. 

So, for summary, we have MRI evidence of increased brain growth across the brain itself, resulting in larger, more dense gray matter within the brain across the board, including those regions protected by the blood brain barrier where ingested or injected glutamate cannot reach once the blood-brain barrier is fully developed (Sahai, Glutamate in the mammalian CNS, European Archives of Psychiatry and Clinical Neuroscience, Volume 240, Number 2 / November, 1990).

Of course, the blood-brain barrier is not fully developed until an infant is 6 months of age (Rodier, Developing Brain as a Target of Toxicity, Environmental Health Perspectives, Vol. 103, Supplement 6 (Sep., 1995), pp. 73-76). But that would at least suggest that any exposure to glutamate after 6 months would have no effect on the growth of the brain, even if there were research to prove glutamate caused brain growth instead of brain damage as presented by Dr. Olney's findings.  Luckily, all food that infants eat up to and past age 6 months has had MSG removed thanks to the work of Dr. Olney.

References to the Chromosome 11 and neurexin1 changes and their relationship with autism have also been brought up in arguments in the dangers of MSG. It is interesting, but keep in mind that glutamate is the most prevalent neurotransmitter in the brain. So a gene that effects neurotransmissions can effect the levels of glutamate in the brain as it is being transmitted. This still doesn't link the ingestion of glutamate to increased brain growth. This actually is more likely to be linked with Fragile X Syndrome. 

Fragile X Syndrome has a unique property that does not allow a neuron to "turn off" their synaptic firings, which cause an overload, and as such causes autistic-like behavior. Glutamate is the transmitter, so if increased glutamate is released by the neuron is causes the neuron to overload, causing damage (not brain growth). So that would be another issue entirely (still worthy of note, however, and reason enough to pursue reduced usage of MSG in the food supply). 

Another argument made to link MSG to autism is the observed decrease of autism-like symptoms when patients remove gluten or cassein from their diet.  This actually refers to the ingestion of propionic acid, which then cause autism-like symptoms. This acid can be produced by a bacteria which ingests gluten and cassein that resides in the gut. The results of injecting this acid directly into the brain caused inflammatory processes, and as such caused autism-like behavior. It is also important to note that propionic acid is a simple fatty acid, and not a form of glutamate.

Now propionic acid in most vertebrates is carboxylated to D-methylmalonyl-CoA, which is isomerised to L-methylmalonyl-CoA. A vitamin B12-dependent enzyme catalyzes rearrangement of L-methylmalonyl-CoA to succinyl-CoA. The inability to process propionic acid could be a cause of what I like to call "allergy autism" or autistic behavior due to an allergic reaction. It would also require propionic acid to be able to cross the blood-brain barrier as a lipid soluble substance. That could be possible, as I don't have enough knowledge of the properties of propionic acid, so I cannot disprove the hypothesis.  But it results in a temporary state, and the patient recovers once the propionic acid is no longer in contact with the brain.

Also, with regards to the blood-brain barrier permeability: it is possible to have a damaged blood-brain barrier and make it more permeable. Common causes are infant rubella, heavy metal exposures, and exposure to alcohol for the developing brain (Rodier, Developing Brain as a Target of Toxicity, Environ Health Perspect 1 03(Suppl 6):73-76 (1995)). Though proper hydration can stem or reverse the increased permeability within the blood-brain barrier (McCall et al, Monosodium glutamate neurotoxicity, hyperosmolarity, and blood-brain barrier dysfunction, Neurobehav Toxicol. 1979 Winter;1(4):279-83). 

So the problem I have is finding that clinical link between glutamate exposure at an early age and the increased brain growth.  So again my request still stands: Is there any clinical evidence that supports neuron growth in the brain (and not sensory neuron growth) as a direct response to increased glutamate exposure? That is the missing piece of the puzzle that I need in order to support the theory of MSG as the cause of autism. As stated earlier, according to Olney’s research, MSG only seems to cause damage to the hypothalamus and retina tissue. No increase in neuron growth or decrease in neuronal pruning has been recorded as far as I can find in the stacks.

So my findings are thus:  MSG is bad, and for many people it can be disruptive to their lives.  It should be removed from the food supply in all it's forms.  This also means that food processing companies will need to actually work to make their food both tasty and safe.  Now there is a concept.  Thank goodness I'm working on my urban farming project to do just that:  make food that tastes better without additives.

But other than general health hazards, there is no concrete link between ingesting MSG and the development of autism.  The only time children could possibly be exposed to MSG past the blood-brain barrier would be before they are 6 months old when the barrier is not yet fully developed, and Dr. Olney has already seen to their protection since the 1970's.  It just seems to me that genetics remains the best answer, providing the most concrete clinical results.

As always, I welcome any clinical studies or rebuttals that are backed with clinical research!  I love to learn new things.